Levamisole and Fluorouracil for Adjuvant Therapy of Resected Colon Carcinoma

• Published in: The New England journal of medicine Vol. 322; no. 6; pp. 352 - 358
• Main Authors: Moertel, Charles G, Fleming, Thomas R, Macdonald, John S, Haller, Daniel G, Laurie, John A, Goodman, Phyllis J, Ungerleider, James S, Emerson, William A, Tormey, Douglas C, Glick, John H, Veeder, Michael H, Mailliard, James A
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 08-02-1990
• Subjects: 5-Fluorouracil; Adjuvant therapy; Adjuvants; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer therapies; Carcinoma - mortality; Carcinoma - pathology; Carcinoma - therapy; Chemotherapy; Colon cancer; Colonic Neoplasms - mortality; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Colorectal cancer; Combined Modality Therapy; Dermatitis; Diarrhea; Family medical history; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Humans; Immunotherapy; Invasiveness; Leukopenia; Levamisole; Levamisole - administration & dosage; Levamisole - adverse effects; Levamisole - therapeutic use; Lymphatic Metastasis; Lymphatic system; Male; Medical prognosis; Medical research; Metastasis; Middle Aged; Nausea; Neoplasm Staging; Oncology; Patient Compliance; Postoperative Care; Radiography; Random Allocation; Stomatitis; Surgery; Vomiting
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM199002083220602

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B
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) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2).
Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P<0.0001). The overall death rate was reduced by 33 percent (P ≈ 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B
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disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone — i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen.
We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice. (N Engl J Med 1990; 322:352–8.)
THIS year, cancer of the colon will afflict over 100,000 persons in the United States.
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As a cause of death due to cancer, it is second only to lung cancer. There is no established means of preventing colon cancer, and there is no reliable and cost-effective means of screening to ensure early diagnosis. In the main, symptomatic patients must be treated as they present themselves, and in half of them cure has unfortunately not been possible. However, in about 80 percent of patients the diagnosis is made at a stage when all apparent diseased tissue can be surgically removed. In . . .